ABSTRACT, Tumor Microenvironment and Metastasis Program (TMM) The Tumor Microenvironment and Metastasis Program (TMM) is a highly interactive Program in which members combine basic, fundamental research expertise to understand the biology of cancer cell autonomous effects in relation to paracrine actions and specific components of the tumor microenvironment (TME) within the primary tumor and at distant metastatic sites and to study the systemic effects of those interactions. The basic work of TMM in predominately ?solid? tumors mirrors the basic research in ?liquid tumors? conducted by HHM which provides the backdrop for translating their findings into the clinic through collaborations with the clinical and translational members of EDT and CPC. Understanding the factors released by the TME into the systemic circulation will provide novel diagnostic strategies, whereas understanding how the TME nurtures cancer cells to enhance invasion and the respective clinical sequelae, will lead to new cancer prevention and treatment strategies. The goals of TMM are to translate discoveries of the pathobiology of solid tumors, the TME, and systemic effects of metastases into new cancer targets and novel therapies, so as to prevent metastases and sequelae. TMM advances this vision by focusing on two overarching themes: Theme 1 is focused on cancer cell-stroma interactions and their roles in cancer initiation, progression, and metastasis. These interactions involve TME components such as cancer-associated fibroblasts, myeloid derived suppressor cells, macrophages, T and B lymphocytes and the extracellular matrix; Theme 2 encompasses the systemic effects of metastases and the mechanisms that contribute to perturbations in muscle, bone and cognitive functions and respective clinical sequelae. During the past five years, there have been several notable successes, including the funding of a SPORE in hyperactive Ras signaling led by work of Dr. Wade Clapp, further development of working groups in cancers of the pancreas, ovary, and prostate, resulting in increased funding in these areas; and new insight into musculoskeletal effects of cancer metastasis. Several members from the former Breast Cancer Program were incorporated into TMM to enhance research expertise in solid cancers. Retreats foster focused, in depth collaborations. TMM has hosted visiting experts and recruited faculty members with expertise based on needs identified at the annual retreats. TMM has 28 Full and 8 Associate Members, representing 17 Departments and 5 Schools on the campuses of Indiana University School of Medicine, Indiana University- Purdue University Indianapolis (IUPUI), and IU Bloomington. The Program has $9.1M in total direct funding (20% increase since 2013), and $6.8M in peer-reviewed funding, with $2.4M from the NCI and $1.8M from other NIH Institutes. Over the past funding period, TMM members have authored 394 publications (18% intra- programmatic, 26% inter-programmatic, and 64% inter-institutional collaborations) and have 17 multi-PI grants including six inter-institutional and eight inter-programmatic (EDT-5, HHM-2 and CPC-1) reflecting strong collaborations through local, national and international networking.